1. Field of the Invention
The present invention relates generally to biopolymer probes immobilized on the surface of a substrate.
2. Description of the Prior Art
New methods for genetic screening and sequencing are based on the hybridization of surface immobilized single-stranded oligonucleotides, or DNA probes. Thiol-derivatized, single-stranded DNA has been used to model hybridization reactions at surfaces. For example, Lee et al. have described covalently attaching thiolated DNA to derivatized silane layers on silica for use in atomic force microscopy studies (Lee et al., "Direct Measurement" in Science, (1994), 266, 771-773). Okahata et al. have prepared a monolayer consisting of thiol-derivatized DNA 10-mers on gold, and measured the mass changes during hybridization using a quartz crystal microbalance (Okahata et al., "Hybridization of Nucleic Acids Immobilized on a Quartz Crystal Microbalance" in J. Amer. Chem. Soc., (1992), 114, 8299-8300). Leavitt et al. describe modifying the phosphate group of the nucleotide backbone with a sulfur group which is adsorbed directly on the surface (Leavitt et al., "Angle-Dependent X-ray Photoelectron Spectroscopy and Atomic Force Microscopy of Sulfur-Modified DNA on Au(111)" in J. Phys. Chem., (1994), 98, 8742-8746).
A problem with all of these prior methods is that is that the DNA can interact strongly with the gold surface, resulting in probes with low hybridization activity. In addition, the prior methods do not permit facile control of the surface coverage of DNA probes.